MYBL2/CREB1-Dependent Distinct FoxA1 Cistrome Directs G1/S Cell Cycle Progression in Androgen-Independent Prostate Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26329 | GEO | 2011/12/08
SECONDARY ACCESSION(S): PRJNA136905
REPOSITORIES: GEO
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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this work is comprehensive analysis of target genes co-regulated by CREB1 and FoxA1 in prostate cancer cell models, tissues, and circulating tumor cells (CTCs). Expression of CREB1/FoxA1 target genes corresponds with disease recurrence and aggressive clinical features. Methods: LNCaP cells between passage number 32-34 and abl between 62-64 were used for assay. For RNA-seq, cells are transfected with FoxA1,CREB1 specific or nonspecific siRNA and total RNA is extracted with Qiangen RNeasy Mini kit(cat 74104) and library is generated with TruSeq RNA Sample Preparation Kit v2 from Illumina(cat RS-122-2001). For Chip-seq, LNCaP cells between passage number 32-34 and abl between 62-64 were used for assay. After crosslinking with 1% formaldehyde, ChIP was performed. the ChIP producted was further used to generate library with illumina ChIP-seq kit. Hi-seq 2500 was used for sequencing and the data was analyzed by MACs for peaks. LNCaP cells and LNCaP cells were used as cell model. Library was sequenced using Illumina HISeq 2500.
2016-01-13 | E-GEOD-63034 | biostudies-arrayexpress
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this work is comprehensive analysis of target genes co-regulated by CREB1 and FoxA1 in prostate cancer cell models, tissues, and circulating tumor cells (CTCs). Expression of CREB1/FoxA1 target genes corresponds with disease recurrence and aggressive clinical features. Methods: LNCaP cells between passage number 32-34 and abl between 62-64 were used for assay. For RNA-seq, cells are transfected with FoxA1,CREB1 specific or nonspecific siRNA and total RNA is extracted with Qiangen RNeasy Mini kit(cat 74104) and library is generated with TruSeq RNA Sample Preparation Kit v2 from Illumina(cat RS-122-2001). For Chip-seq, LNCaP cells between passage number 32-34 and abl between 62-64 were used for assay. After crosslinking with 1% formaldehyde, ChIP was performed. the ChIP producted was further used to generate library with illumina ChIP-seq kit. Hi-seq 2500 was used for sequencing and the data was analyzed by MACs for peaks.
2016-01-13 | GSE63034 | GEO
Project description:FOXA1 is a pioneer factor that is important in hormone dependent cancer cells to stabilise nuclear receptors, such as estrogen receptor (ER) to chromatin. FOXA1 binds to enhancers regions that are enriched in H3K4mono- and dimethylation (H3K4me1, H3K4me2) histone marks and evidence suggests that these marks are requisite events for FOXA1 to associate with enhancers to initate subsequent gene expression events. However, exogenous expression of FOXA1 has been shown to induce H3K4me1 and H3K4me2 signal at enhancer elements and the order of events and the functional importance of these events is not clear. We performed a FOXA1 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells in order to identify FOXA1 interacting partners and we found histone-lysine N-methyltransferase (MLL3) as the top FOXA1 interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition, in line with our observation that MLL3 associates with an enhancer specific protein. We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.
2016-12-12 | PXD005253 | Pride
Project description:To define the function of FOXA1-S331 phosphorylation, we substituted S331 in both FOXA1 alleles for alanine in C4-2 cells via CRISPR/Cas9-based gene editing, thereby generating phosphorylation incompetent FOXA1S331A cells. We directly assessed the consequences of phospho-incompetent FOXA1S331A mutation on the transcription profile, chromatin deposition of FOXA1, AR, H3K27ac and chromatin accessibility.
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Project description:To define the function of FOXA1-S331 phosphorylation, we substituted S331 in both FOXA1 alleles for alanine in C4-2 cells via CRISPR/Cas9-based gene editing, thereby generating phosphorylation incompetent FOXA1S331A cells. We directly assessed the consequences of phospho-incompetent FOXA1S331A mutation on the transcription profile, chromatin deposition of FOXA1, AR, H3K27ac and chromatin accessibility.
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Project description:To define the function of FOXA1-S331 phosphorylation, we substituted S331 in both FOXA1 alleles for alanine in C4-2 cells via CRISPR/Cas9-based gene editing, thereby generating phosphorylation incompetent FOXA1S331A cells. We directly assessed the consequences of phospho-incompetent FOXA1S331A mutation on the transcription profile, chromatin deposition of FOXA1, AR, H3K27ac and chromatin accessibility.
2024-05-01 | GSE232124 | GEO
Project description:MYBL2 is a transcription factor that has either pro-survival or anti-survival functions in a cell-type specific manner. Overexpression of MYBL2 is associated with worse survival of lung adenocarcinoma, but the mechanism by which it regulates transcription has not yet been elucidated. In this study, we found that MYBL2 mainly binds to the promoters of highly expressed genes in lung adenocarcinoma cells using ChIP-seq. Using knock-down and RNA-seq approach, we identified over a thousand of genes deregulated by MYBL2. By integrating ChIP-seq and RNA-seq data, we identified target genes of MYBL2. We revealed that FOXM1 is regulated by MYBL2 in lung adenocarcinoma cells, and FOXM1 binding sites are largely shared with MYBL2 binding sites. We treated lung adenocarcinoma cells with FDI-6, a known FOXM1 inhibitor and investigated the effect of FDI-6 in transcriptional regulation of MYBL2 and FOXM1. We found that CENPA is one of the key genes regulated by MYBL2 and FOXM1, and that it can be inhibited by FDI-6. Our signaling pathway analysis results revealed that MYBL2 and FOXM1 activate cell-cycle genes, suggesting that MYBL2 and FOXM1 act as oncogenic transcription factors in lung adenocarcinoma cells and FDI-6 could be a potential treatment of the disease.
2022-11-02 | GSE201271 | GEO
Project description:MYBL2 is a transcription factor that has either pro-survival or anti-survival functions in a cell-type specific manner. Overexpression of MYBL2 is associated with worse survival of lung adenocarcinoma, but the mechanism by which it regulates transcription has not yet been elucidated. In this study, we found that MYBL2 mainly binds to the promoters of highly expressed genes in lung adenocarcinoma cells using ChIP-seq. Using knock-down and RNA-seq approach, we identified over a thousand of genes deregulated by MYBL2. By integrating ChIP-seq and RNA-seq data, we identified target genes of MYBL2. We revealed that FOXM1 is regulated by MYBL2 in lung adenocarcinoma cells, and FOXM1 binding sites are largely shared with MYBL2 binding sites. We treated lung adenocarcinoma cells with FDI-6, a known FOXM1 inhibitor and investigated the effect of FDI-6 in transcriptional regulation of MYBL2 and FOXM1. We found that CENPA is one of the key genes regulated by MYBL2 and FOXM1, and that it can be inhibited by FDI-6. Our signaling pathway analysis results revealed that MYBL2 and FOXM1 activate cell-cycle genes, suggesting that MYBL2 and FOXM1 act as oncogenic transcription factors in lung adenocarcinoma cells and FDI-6 could be a potential treatment of the disease.
2022-11-02 | GSE201270 | GEO
Project description:A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these M-bM-^@M-^\sub-haploinsufficientM-bM-^@M-^] cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases. Cryopreserved CD34+ bone marrow were cultured for 24 hours, transduced with shRNA-encoding vectors and selected with Puromycin for 48 hours. Vectors shRNA 1-8 are specifically targeting MYBL2, vectors shRNA A-D encoded an irrelevant control shRNAs and one culture was left untreated (no shRNA). Cells were harvested after Puromycin selection and total RNA was prepared using Trizol (LifeTechnologies).
2013-09-15 | E-GEOD-43400 | biostudies-arrayexpress
Project description:A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these M-bM-^@M-^\sub-haploinsufficientM-bM-^@M-^] cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases. Total RNA was prepared from CD34+ bone marrow cells obtained from MDS patients or healthy controls.
2013-09-15 | E-GEOD-43399 | biostudies-arrayexpress